An adipose tissue galectin controls endothelial cell function via preferential recognition of 3-fucosylated glycans

Upon overnutrition, adipocytes activate a homeostatic program to adjust anabolic pressure. An inflammatory response enables adipose tissue (AT) expansion with concomitant enlargement of its capillary network, and reduces energy storage by increasing insulin resistance. Galectin-12 (Gal-12), an endog...

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Bibliographic Details
Authors: Maller, Sebastian Matias, Cagnoni, Alejandro, Bannoud, Nadia, Sigaut, Lorena, Pérez Sáez, Juan Manuel, Pietrasanta, Lia, Yang, Rio Yao, Liu, Fu Tong, Croci Russo, Diego Omar, Di Lella, Santiago, Sundbland, Victoria, Rabinovich, Gabriel Adrián, Mariño, Karina Valeria
Format: article
Status:Published version
Publication Date:2019
Country:Argentina
Institution:Consejo Nacional de Investigaciones Científicas y Técnicas
Repository:CONICET Digital (CONICET)
Language:English
OAI Identifier:oai:ri.conicet.gov.ar:11336/157043
Online Access:http://hdl.handle.net/11336/157043
Access Level:Open access
Keyword:ADIPOSE TISSUE
ANGIOGENESIS
GALECTINS
GLYCOSYLATION
https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
Description
Summary:Upon overnutrition, adipocytes activate a homeostatic program to adjust anabolic pressure. An inflammatory response enables adipose tissue (AT) expansion with concomitant enlargement of its capillary network, and reduces energy storage by increasing insulin resistance. Galectin-12 (Gal-12), an endogenous lectin preferentially expressed in AT, plays a key role in adipocyte differentiation, lipolysis, and glucose homeostasis. Here, we reveal biochemical and biophysical determinants of Gal-12 structure, including its preferential recognition of 3-fucosylated structures, a unique feature among members of the galectin family. Furthermore, we identify a previously unanticipated role for this lectin in the regulation of angiogenesis within AT. Gal-12 showed preferential localization within the inner side of lipid droplets, and its expression was upregulated under hypoxic conditions. Through glycosylation-dependent binding to endothelial cells, Gal-12 promoted in vitro angiogenesis. Moreover, analysis of in vivo AT vasculature showed reduced vascular networks in Gal-12-deficient (Lgals12-/-) compared to wild-type mice, supporting a role for this lectin in AT angiogenesis. In conclusion, this study unveils biochemical, topological, and functional features of a hypoxia-regulated galectin in AT, which modulates endothelial cell function through recognition of 3-fucosylated glycans. Thus, glycosylation-dependent programs may control AT homeostasis by modulating endothelial cell biology with critical implications in metabolic disorders and inflammation.

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